The goal of this research project is to develop a new generation of denture-base polymers that could control microbial colonization and prevent denture-induced stomatitis. These new polymers will be synthesized by the incorporation of phosphate groups within poly (methyl methacrylate) [PMMA] to prevent denture infection. Phosphate groups in the new polymers will provide the required anionic surface for the salivary cationic antimicrobials to be selectively adsorbed onto the denture surface. This will result in the formation of a defense pellicle layer on the denture surface. The currently available PMMA, due to the absence of ionic surface and the defense denture pellicle component, does not inhibit microbial colonization This research project involves: 1) Synthesis of phosphated PMMAs containing varied amounts of phosphate groups and non-phosphated PMMA and characterization of polymers;2) Assessment of the efficacy of this polymer to adsorb and desorb salivary antimicrobials using histatin 5 and a defensin fragment;3)Determination of the microbicidal activity of antimicrobials adsorbed phosphated polymers using Candida albicans, Streptococcus Sanguis, Streptococcus oralis, Streptococcus gordonii and Streptococcus mutans;4) Delineation of the physical and mechanical properties of polymers that exhibit high affinity for salivary antimicrobials, and inhibit microbial adhesion to the polymer surface following the ADA/ISO guidelines;5) Assessment of the in vitro cytotoxicity of polymer specimens against a human oral epithelial cell line, human primary gingival fibroblast cells, and the standard L-929 cell line to ascertain the safety requirements for Dental materials. Relevance: This proposed research will identify new, safe and affordable phosphated PMMA polymers that could serve as denture-base or denture base lining materials for the prevention and treatment of denture infection. These new polymers will exhibit physical, mechanical and biological properties comparable to those of normal oral surfaces, and will have significant impact on the expenses involved in the treatment of denture-induced infection associated with the existing PMMA polymer. The use of these new polymers could improve the oral health of a significant population of prosthesis users. The phosphated PMMA polymers could have great potential for clinical and commercial applications.